Adherens junctions are multiprotein complexes that mediate cellular adhesion and cell-cell communication, processes that are required for the formation of organized tissues. Associated with adherens junctions are a diverse set of cytoplasmic proteins termed catenins. Catenins perform a structural role in linking adherens junctions to the actin cytoskeleton, and are also involved in transducing cell-cell signals. The long term goal of this research is to identify the functions performed by pl2O, a recently identified catenin associated with adherens junctions, using the Drosophila model system. The specific aims of the proposal are: l) Examine the developmental role of dp12O by generating mutations in the dpl2O gene and characterizing the resulting phenotypes, 2) Identify and characterize proteins that interact with dpl2O. Vertebrate pl2O was originally identified as a substrate of the src oncogene and pl2O phosphorylation was correlated with adherens junction breakdown and cell transformation. In addition, a pl2O family member, delta-catenin, was recently shown to interact with Presenilin I protein; Presenilins are mutated in families with early-onset Alzheimer's disease. To identify pl20 function, a genetic screen will be performed to identify multiple new dpl2O alleles. Mutants will be analyzed for cell adhesion defects, Wingless signaling defects, and neural developmental defects. Using molecular, biochemical, and cell biological approaches, proteins that interact with dp12O will be identified and the functional consequences of these interactions will be analyzed in vivo. Learning about dp12O function and identifying its protein binding partners will provide new insights regarding the key developmental signaling pathways, Wingless and Notch. In addition, dp12O mutants may be useful models to study abnormal cell behavior that may lead to cancer or provide insights into the pathogenesis of Alzheimer's disease.